Degradable thermosensitive injectable hydrogels with two-phase composite structure from aqueous solutions of poly(N-isopropylacrylamide-co-5,6-benzo-2-methylene-1,3-dioxepane)-poly(ethylene glycol) triblock copolymers and biopolymers

Novel degradable thermosensitive injectable hydrogels with two-phase composite structure and improved mechanical strength were prepared by adding sodium alginate or dextran to the aqueous solution of a hydrolytically degradable ABA triblock copolymer with poly(ethylene glycol) middle block and poly(N-isopropylacrylamide) containing in-chain ester groups as side blocks. The two-phase structure, demonstrated by SEM measurements, resulted as a consequence of the triblock copolymer-biopolymer incompatibility. The biopolymer addition decreased the gelation temperature (T-gel) and strongly improved the viscoelastic properties of the resulted hydrogel, whose behavior at 37 A degrees C turned from liquid-like to a gel-like one. The composite hydrogels displayed low gelation time and high stability (i.e., no sign of syneresis after 42 days) at 37 A degrees C. They partially degraded in PBS at 37 A degrees C as a consequence of the hydrolysis of the in-chain ester groups of the thermosensitive blocks, leading to a progressive increase of T-gel and decrease of gel strength. The ability of the composite hydrogels to control the release rate of drugs was tested in PBS at 37 A degrees C by employing 5-flurouracil (5FU) and chlorambucil (CLB) as model drugs with different hydrophilicity. 5FU displayed a pretty fast release rate, unlike CLB whose release rate was much slower, no effect of the biopolymer nature being noticed. During the drug release experiments, the hydrogels showed a moderate mechanical stability, although higher than in the absence of the biopolymer, and also progressively dissolved within 12-17 days because of the hydrogel erosion phenomenon, probably accelerated by the partial degradation of the triblock copolymer.